UPDATE Newsletter November 2018

The NTP Interagency Center for the Evaluation of Alternative Toxicological Methods

By Catherine Sprankle

International Meeting Considers New Approaches to Test Method Validation

On October 23-24, NICEATM Director Warren Casey joined scientists from around the world at a meeting on “Validation and Establishing Scientific Confidence” at the European Commission Joint Research Centre in Ispra, Italy.

The meeting was organized by the International Cooperation on Alternative Test Methods (ICATM). Representatives from ICATM participating organizations in the United States, Canada, European Union, Japan, South Korea, and Brazil attended, along with representatives of the European Chemicals Agency, the European Food Safety Agency, the German Federal Institute for Risk Assessment, the Singapore Agency for Science, Technology and Research, and the Organisation for Economic Co-operation and Development (OECD).

Validation establishes the reliability and relevance of a test method for an intended application. However, it is difficult to apply traditional validation practices to new approaches to chemical safety testing, such as computational methods and defined approaches that combine multiple types of assay data. Participants at the October 23-24 meeting identified key questions to consider in addressing this issue. They discussed a number of challenges to address in evolving the process of validation, including demonstrating relevance without animal data and establishing more efficient validation procedures. Validation elements identified for particular consideration included reference chemical lists and independent peer review.

Following this meeting, Casey attended a coordination meeting of ICATM participating organizations in Ispra on October 25. In addition to sharing updates on their organizations’ activities, attendees at this meeting continued discussions from the October 23-24 meeting. As a first step towards addressing the identified issues, ICATM representatives agreed that they would conduct a detailed review of OECD Guidance Document 34, the current standard for validation of chemical safety test methods. The goal of this review is to identify more specific issues to be addressed in moving forward with new approaches to validation.

Updates to Integrated Chemical Environment

Successful computational toxicology projects depend on freely available, high-quality data that are formatted for use in computational workflows. The NICEATM Integrated Chemical Environment (ICE) resource provides data from NICEATM and its partners as well as other resources and tools in an environment designed to support chemical safety assessment and new method development.

A major update to ICE was launched on September 28. This and other recent updates have:

Expanded physicochemical property predictions to include over 720,000 chemicals using an updated set of predictive models (Mansouri et al. 2018)

Updated the curated high throughput screening data coming from the Tox21 initiative to include increased curation and the most up-to-date data release

Added new workflows to enable in vitro to in vivo extrapolation (Casey et al. 2018), construction of machine-learning models to predict chemical hazard, and chemical list characterization using physicochemical properties to relate chemicals

NICEATM and the International Alliance for Biological Standardization co-organized an October 16-17 workshop “Implementing Non-animal Approaches to Human and Veterinary Vaccine Testing: Achieving Scientific and Regulatory Success for Rabies and Beyond” at the National Institutes of Health (NIH) in Bethesda, Maryland. Over 60 scientists from government, academia and industry gathered to develop recommendations to advance alternative methods for human and veterinary rabies vaccine testing.

Presentations on the first day of the workshop detailed the current state of the science of non-animal alternatives to traditional rabies vaccine potency and safety tests. On day two, separate breakout group discussions focused on the steps necessary for implementing alternatives for veterinary and human rabies vaccine potency testing. Participants identified actions and data still needed to achieve this, and laid the foundation for a roadmap towards successful implementation. Meeting outcomes and associated recommendations will be summarized in a report in the journal Biologicals.

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